Dynamics of capillary blood flow responses to acute local changes in oxygen and carbon dioxide concentrations

Objectives: We aimed to quantify the magnitude and time transients of capillary blood flow responses to acute changes in local oxygen concentration ([O-2]), and carbon dioxide concentration ([CO2]) in skeletal muscle. Additionally, we sought to quantify the combined response to both low [O-2] and high [CO2] to mimic muscle microenvironment changes at the onset of exercise. Methods: 13 Sprague Dawley rats were anaesthetized, mechanically ventilated, and instrumented with indwelling catheters for systemic monitoring. The extensor digitorum longus muscle was blunt dissected, and reflected over a microfluidic gas exchange chamber in the stage of an inverted microscope. Four O-2 challenges, four CO2 challenges, and a combined low O-2 (7-2%) and high CO2 (5-10%) challenges were delivered to the surface with simultaneous visualization of capillary blood flow responses. Recordings were made for each challenge over a 1-min baseline period followed by a 2-min step change. The combined challenge employed a 1-min [O-2] challenge followed by a 2-min change in [CO2]. Mean data for each sequence were fit using least-squared non-linear exponential models to determine the dynamics of each response. Results: 7-2% [O-2] challenges decreased capillary RBC saturation within 2 s following the step change (46.53 +/- 19.56% vs. 48.51 +/- 19.02%, p < 0.0001, tau = 1.44 s), increased RBC velocity within 3 s (228.53 +/- 190.39 mu m/s vs. 235.74 +/- 193.52 mu m/s, p < 0.0003, tau = 35.54 s) with a 52% peak increase by the end of the challenge, hematocrit and supply rate show similar dynamics. 5-10% [CO2] challenges increased RBC velocity within 2 s following the step change (273.40 +/- 218.06 mu m/s vs. 276.75 +/- 215.94 mu m/s, p = 0.007, tau = 79.34s), with a 58% peak increase by the end of the challenge, supply rate and hematocrit show similar dynamics. Combined [O-2] and [CO2] challenges resulted in additive responses to all microvascular hemodynamic measures with a 103% peak velocity increase by the end of the collection period. Data for mean responses and exponential fitting parameters are reported for all challenges. Conclusion: Microvascular level changes in muscle [O-2] and [CO2] provoked capillary hemodynamic responses with differing time transients. Simulating exercise via combined [O-2] and [CO2] challenges demonstrated the independent and additive nature of local blood flow responses to these agents.

Automated summary

This study aimed to quantify the blood flow responses in skeletal muscle capillaries to changes in oxygen and carbon dioxide concentrations. The results showed that oxygen and carbon dioxide changes had different time transients on blood flow velocity, red blood cell saturation, and hematocrit. Additionally, the combined challenge of low oxygen and high carbon dioxide resulted in additive responses in these hemodynamic measures.